Marijuana extracts can impair the survival of certain types of cancer cells and inhibit their spread, according to a recent study. But the effects of those extracts vary significant based on their specific chemical makeup.
Researchers found that treating cancer cells with isolated ingredients in cannabis, such as THC alone, does not appear to be especially effective—but full cannabis extracts showed more promise. However, with the plant containing hundreds of compounds that appear in different concentrations across strains and preparations, researchers had their work cut out for them in investigating how various cannabinoid combinations treated different types of cancer cells.
The team tested the antitumor effects of 12 whole cannabis extracts on 12 human cancer cell lines in order to “determine whether whole cannabis preparations with specific phytocannabinoid profiles could be advantageous as therapy for certain cancer sub-types.” The findings were published in the journal Oncotarget.
“Our results show that specific cannabis extracts impaired the survival and proliferation of cancer cell lines as well as induced apoptosis.”
Each cell sample was treated with a marijuana extract in increasing doses (2-10 µg/ml) over the course of 24 hours. There were five preparations of cannabis that proved especially potent for a wide range of cancer types but, in general, the study shows there’s significant variability in effectiveness for different cancer types—even when the cancers originated in the same organ.
For example, two distinct forms of prostate cancer cells were found to be most sensitive to entirely different marijuana extracts.
The cannabis preparations also ranged widely in their effectiveness in preventing the proliferation of cancer cells. When applied to multiplying cells, there were three extracts that reduced the growths to 37-51 percent of their original size, compared to 68 percent for the control group. But there were other extracts that failed to reduce the spread in a statistically significant manner.
Some commonalities shared among the most potent cannabis extracts include a high concentration of THC and large amounts of phytocannabinoids in their decarboxylated form.
“Taken as a whole, we concluded that medical cannabis does not consist of a single therapeutic agent but rather a heterogeneous array of treatments,” the researchers wrote. “We propose that the fate of specific cancer cells following cannabis extract application is dependent upon the synergistic effects of its phytocannabinoid composition, concentration applied, along with the cell specific characteristics (e.g. cannabimimetic receptor expression).”
“This study demonstrates the anti-cancer activity of various whole cannabis extracts on a set of human cancer cell lines.”
The study concluded that “cannabis extracts were very potent in producing cell death and some of these extracts were of [THC]-rich type” and that, as previous studies have indicated, “using whole cannabis extracts is more effective in inducing cancer cell death than applying pure [THC] on the studied cells lines.”
“Furthermore, not all [THC]-rich extracts produce the same effects when applied at the same concentrations on a specific cancer cell line,” the study authors wrote. “These findings indicate that compounds other than [THC] in these extracts might act together in a polypharmacology way and determine the extract efficacy as antitumor agents.”
Interestingly, the researchers also theorized that the the “presence or absence of [cannabinoid receptors] in the tested cell lines may explain the differential potency of the extracts towards reducing cell survival.”
The team called for further research into the “specific properties and mechanisms of cancer cell insensitivity to cannabis extract effects.”
“We hope that this study will lay the groundwork for future preclinical studies and randomized controlled clinical trials in order to provide evidence for effective cannabis treatments for many cancer subtypes,” they concluded.
Photo courtesy of Evan Johnson.
Legal Marijuana States Had Fewer Vaping-Related Lung Injuries, Study Finds
People in states where recreational marijuana is legal were significantly less likely to experience vaping-related lung injuries than those in states where cannabis is prohibited, according to a new study published in an American Medical Association journal.
The finding seems to affirm what many reform advocates said during the peak of the e-cigarette or vaping product use-associated lung injury (EVALI) crisis last year. With thousands being hospitalized over EVALI, it became clear that contaminated vape cartridges were the source and that contamination was more common in illicit, unregulated markets where consumers can’t walk into retail stores and buy tested and labeled marijuana products.
By analyzing Centers for Disease Control and Prevention (CDC) data on EVALI cases, the prevalence of e-cigarette use and the population in each state from June 2019 to January 2020, researchers were able to confirm that.
The research letter, published by the JAMA Network Open on Monday, shows that states with recreational marijuana shops had 1.7 EVALI cases per million population compared to 8.1 cases per million in prohibition states. There was no statistically significant difference between criminalized and medical cannabis states, which experienced 8.8 cases per million population.
“The data suggest that EVALI cases were concentrated in states where consumers do not have legal access to recreational marijuana dispensaries,” the letter states. “This association was not driven by state-level differences in e-cigarette use, and EVALI case rates were not associated with state-level prevalence of e-cigarette use. One possible inference from our results is that the presence of legal markets for marijuana has helped mitigate or may be protective against EVALI.”
“Recreational marijuana states had among the lowest EVALI rates of all states.”
Cross-sectional study finds states with legal recreational marijuana had fewer cases of e-cig/vaping associated lung injury #EVALI. @aaronecarroll @ajhollingsworth @AshleyCBradford @coady_wing #VisualAbstract https://t.co/9dXGchag16 pic.twitter.com/nIoeV7v39b
— JAMA Network Open (@JAMANetworkOpen) April 7, 2020
While the researchers said the reason for the association isn’t clear yet, they surmised that it’s “possible that in recreational states, people tend to purchase marijuana products at legal dispensaries, which may be less likely to sell the contaminated products that are thought to cause EVALI.”
That has been the working theory of many industry observers, who have argued that legalization is an important safeguard to public health by ensuring compliance with quality control standards in cannabis products. It should be noted, however, that there are select reports of instances where people seemed to develop a lung injury after obtaining marijuana vaping products from licensed dispensaries in Oregon.
“It appears states that have legal access to marijuana have lower rates of EVALI cases, which is consistent with the hypothesis that people have demand for marijuana products, and in states where they don’t have access to them in this regulatory fashion, they end up purchasing them elsewhere,” study co-author Alex Hollingsworth told MedPage Today.
NORML Executive Director Erik Altieri said the findings “come as little surprise.”
“In jurisdictions where cannabis is legally regulated, consumers gravitate toward the above-ground retail marketplace where they can access lab-tested products manufactured by licensed businesses,” he said. “Just like alcohol prohibition gave rise to the illicit production of dangerous ‘bathtub gin,’ marijuana prohibition provides bad actors, not licensed businesses, the opportunity to fulfill consumers’ demand—sometimes with tragic results.”
In a historical commentary on the new study also published by the American Medical Association Journal, a separate set of researchers drew a parallel to the era of alcohol prohibition—from which an underground industry of bootleggers emerged.
“Bootleggers fortified their distillates with methanol to increase apparent potency, causing blindness and death in unwary consumers,” they said, noting that industrial ethanol, which was exempt from prohibition, was sometimes used despite the fact that government officials directed it to be adulterated with poisonous substances to deter consumption. “The resulting concoctions, known as denatured alcohol, were responsible for thousands of deaths during the 14 years that Prohibition was in effect. The history of Prohibition thus serves as a cautionary tale about unintended and unforeseen consequences of legislation regulating substances that affect public health.”
“Bootlegging was rampant and criminal syndicates proliferated, fueling a wave of organized crime.”
Commentary: EVALI rates are lower in states that have legalized recreational marijuana. Is legalizing marijuana protective against EVALI as there is less incentive to dilute THC in states where raw THC material is readily available without legal risk? https://t.co/Bd5Z8wYbjQ
— JAMA Network Open (@JAMANetworkOpen) April 7, 2020
EVALI similarly appears to be strongly associated with a specific contaminant in illicit markets, vitamin E acetate (VEA), which is used to dilute or stretch cannabis concentrates —”a scenario reminiscent of the unscrupulous bootleggers of the Prohibition era.”
“How could a state’s legalization of recreational marijuana inadvertently protect its citizens against EVALI? The obvious answer is that THC-containing vaping products in states where recreational marijuana is legal are uncontaminated with VEA. If so, another question follows: why would THC products in these states be less likely to be contaminated (ie, diluted) with VEA? One salient possibility is that there is less financial incentive to dilute THC concentrates in states where raw THC material is readily available without legal risk and compensatory markup.”
“If THC concentrates are transported from states where they are legal and can be relatively cheaply mass produced (like industrial ethanol stocks during Prohibition) to other states where they are illegal and must be guarded jealously as a rare and precious commodity, there may be a strong economic inducement to dilute them, thereby increasing profits. Thus, legalization of marijuana may have protective local effects but untoward collateral effects.”
President Trump also seemed to pick up on the failure of prohibition during a meeting on the vaping crisis last year. He acknowledged that simply banning the products wouldn’t work, as people would simply move on to the illicit market, where there aren’t regulations.
What’s worse, the conflict between state and federal marijuana laws actually inhibited research into how to address EVALI cases, complicating shipments of vaping specimens, a top CDC official said.
The same official also suggested that federal cannabis regulations could mitigate the vaping problem. Former Food and Drug Administration Commissioner Scott Gottlieb made a similar argument.
This story was updated to include comment from NORML.
Feds Funding Research On How Marijuana Consumers Are Impacted By Coronavirus
A top federal agency is asking researchers to submit grant applications to study how people who consume drugs—particularly those who smoke or vape marijuana or tobacco—are uniquely impacted by a coronavirus infection.
In a notice from the National Institute on Drug Abuse (NIDA) that was published last month, the agency said the rapid spread of the pandemic makes it imperative that researchers identify potential medical complications for people who contract the virus and use substances that could compromise their respiratory system or other health functions.
Two grants have been made available to scientists who are able to investigate these issues.
“As people across the U.S. and the rest of the world prepare for what could be a pandemic of the 2019 novel coronavirus, or COVID-19, the research community should be alert to the possibility that it could affect some populations with substance use disorders or HIV particularly hard,” NIDA said. “Because it attacks the lungs, COVID-19 could be an especially serious threat to those with histories of smoking tobacco or marijuana or of vaping.”
“People who use opioids or methamphetamine may also be vulnerable due to those drugs’ effects on respiratory and pulmonary health and potential effects on immune mechanisms. Likewise, those with HIV may be affected if their immune function is compromised,” the notice continues. “Additional social and environmental factors associated with drug use may worsen the transmission and treatment of COVID-19, especially among individuals who experience homelessness or incarceration, which is more common among those with a substance use disorder.”
NIDA listed a series of research objectives it hopes to expedite, including whether substance use, “especially smoking tobacco or marijuana, vaping, opioids and other drug use,” could be a risk factor in the onset or progression of the coronavirus.
It also wants to generally “understand the respiratory effects” of such behaviors, “in particular those with nicotine, marijuana, opioid, and methamphetamine use disorders.”
The notice also states that the agency is interested in learning about the impact of a coronavirus infection among pain patients who use opioids and those with opioid misuse disorders. NIDA said studies investigating how the virus “influences the outcomes for naloxone interventions for overdose reversal” are also of interest.
The agency will be accepting applications for the grants on a rolling basis through March 31, 2021.
Federal agencies have made a series of requests for scientific submissions on cannabis-related topics in recent months. For example, the Agency for Healthcare Research and Quality put out a call for studies on the impact of marijuana on pain and migraines in January.
Youth Marijuana Treatment Admissions Fell After Legalization, Study Finds
Does legalizing marijuana for adults lead to a tidal wave of teens going to treatment? Not according to a new study out of Temple University, where researchers in fact found decreases in youth admission rates for problem cannabis use in two legal states.
The findings, published this month in the journal Drug and Alcohol Dependence, run counter to speculation from legalization opponents, law enforcement and some public health experts, who have warned that relaxing cannabis laws could lead to an explosion in cannabis use disorders among children. If that’s happening, the study found, treatment admissions data so far show no sign of it.
Examining data from publicly funded substance use treatment facilities, researchers from Temple’s geography and urban studies department, found that youth treatment admissions rates for cannabis use disorder fell sharply between 2008 and 2017, nationally as well as in Colorado and Washington State, which both passed legalization laws in 2012.
“Our results indicate that [recreational marijuana legalization] in Colorado and Washington was not associated with an increase in treatment admissions,” the study concluded. “Rather, we observe a substantial decline in admissions rates across US states, with evidence suggesting a greater decline in Colorado/Washington following RML as compared to non-RML states, though this difference was not significant.”
Co-author Jeremy Mennis, a Temple professor, told Marijuana Moment that the “national decline is pretty dramatic,” noting that on average, youth admissions rates for marijuana fell by nearly half.
“It declined more in Colorado and Washington, but the difference between them and other states was not statistically significant,” he said.
In other words, at least so far, legalization doesn’t seem to have made a particularly big impact on youth admissions rates one way or the other.
“Adolescent treatment admissions for marijuana use did not increase in Colorado and Washington following [recreational marijuana legalization].”
“The admissions rate is initially higher in Colorado/Washington at the beginning of the study period,” Mennis and co-author Gerald Stahler wrote, “but declines more rapidly following [legalization] as compared to the other states.”
As the study notes, if legalizing cannabis for adults were to increase the prevalence of cannabis use disorder among youth, “one potential consequence would be an increased need for treatment.” But that increased need hasn’t been reflected in actual admissions rates.
Still, the researchers are quick to caution that a drop in treatment admissions doesn’t necessarily mean a decrease in problem marijuana use.
“We’re not sure whether cannabis use disorder is declining or just treatment admissions are declining” for some other reason, Mennis said.
Youth cannabis consumption in the U.S. “has not substantially increased over the last 10 years,” he said, but it’s not drastically fallen, either. Yet since about 2011, treatment admissions have steadily declined.
Why the drop in admissions rates? “I don’t know why,” Mennis acknowledged. “This is speculative on my part.”
One possibility is that changing attitudes toward the potential dangers of marijuana have shifted in recent years, making individuals and their loved ones less likely to seek treatment.
“The perception that using marijuana is harmful has declined across the U.S. among youth and adults,” Mennis said, “and this may affect how people view whether their marijuana use is problematic or requires treatment.”
If fewer parents see cannabis as a harmful drug, for example, “they’re probably a lot less likely to see the use of marijuana among their kids as warranting treatment,” he said. “That’s a possibility.”
Reduced stigma around cannabis generally could also be playing a role, he said, with parents perhaps less likely to refer their kids to treatment for simply experimenting with the drug absent other problems connected to such use.
Perhaps the worst-case scenario, the paper says, is that the need for treatment still exists but somehow isn’t being met:
“If [cannabis use disorder] remained stable following [recreational marijuana legalization], or increased, as recent research indicates, the dramatic decline in adolescent treatment admissions we observe in states enacting [recreational marijuana legalization] would suggest an increase in unmet need for treatment, i.e. it may be the case that admissions rates are falling because an increasing proportion of adolescents with CUD are not entering treatment.”
“Cannabis use disorder is a thing, and I think a lot of people are resistant to the idea that it can be a thing. The question is whether cannabis use disorder is actually decreasing,” Mennis said. “If cannabis use is staying the same, then there’s a bigger and bigger gap.”
Studies on cannabis use disorder have arrived at mixed conclusions about whether it’s becoming more or less common as legalization spreads to more states. A study published last year found that, contrary to the expectations of some health experts, the prevalence of cannabis use disorder among frequent cannabis users has actually decreased in recent decades.
Cannabis use disorder “decreased significantly across all ages reporting daily/almost daily cannabis use between 2002-2016,” that study found. “Cannabis dependence prevalence decreased for adolescents and young adults and was stable only among adults ages 26+ reporting daily/almost daily cannabis use.”
Photo courtesy of Martin Alonso